The invention relates to the field of treating HIV with modified T-cells.
In 1984, HIV was shown to be the etiologic agent of AIDS. Since that time, the definition of AIDS has been revised a number of times with regard to what criteria should be included in the diagnosis. However, despite the fluctuation in diagnostic parameters, the simple common denominator of AIDS is the infection with HIV and subsequent development of persistent constitutional symptoms and AIDS-defining diseases such as a secondary infections, neoplasms, and neurologic disease.
HIV is a human retrovirus of the lentivirus group. The four recognized human retroviruses belong to two distinct groups: the human T lymphotropic (or leukemia) retroviruses, HTLV-1 and HTLV-2, and the human immunodeficiency viruses, HIV-1 and HIV-2. The former are transforming viruses whereas the latter are cytopathic viruses.
HIV-1 has been identified as the most common cause of AIDS throughout the world. Sequence identity between HIV-2 and HIV-1 is about 40%, with HIV-2 being more closely related to some members of a group of simian immunodeficiency viruses (SIV).
The main cause of the immune defect in AIDS has been identified as a quantitative and qualitative deficiency in the subset of thymus-derived (T) lymphocytes, the T4 population. This subset of cells is defined phenotypically by the presence of the CD4 surface molecule, which has been demonstrated to be the cellular receptor for HIV. Although the T4 cell is the major cell type infected with HIV, essentially any human cell that expresses the CD4 molecule on its surface is capable of binding to and being infected with HIV.
Previous attempts to treat patients with “designer” T-cells expressing chimeric immune receptors (CIRs) proved unsuccessful. There exists a need in the art for new therapies for HIV. The present invention addresses this issue and offers advantages over previous attempted therapies.